ABSTRACT
Acetylcholine elicits dilatation of rat mesenteric arteries by releasing endothelium-derived hyperpolarizing factor (EDHF) identified as a P450 metabolite of arachidonic acid, epoxyeicosatrienoic acid (EET). This study hypothesizes that free radical species generated as by-products of arachidonic acid metabolism contribute to impaired EDHF-mediated dilatation in deoxycorticosterone acetate (DOCA)-salt induced hypertension. EDHF dilatation was studied in arterial beds isolated from sham and DOCA-salt rats, and perfused (5ml/min) with physiological salt solutions (37 C; bubbled with carbogen) and containing blockers of nitric oxide and prostanoid biosyntheses. EDHF-mediated dilatation to acetylcholine decreased significantly: 28.30.5% (DOCA-salt) vs 88.12.4% (sham); blood pressures were 180 5/1665 (DOCA-salt) vs 1283/1166 (sham), respectively. Arterial microsomes convert 14[C]-arachidonic acid to EETs in the presence of NADPH and generate free radical species as by-products; microsomes of DOCA-salt treated arteries form less (P0.05) EETs, but significantly more free radicals vs microsomes from sham rats. Treatment of DOCA-salt rats with an antioxidant, tempol, alleviates hypertension and improves EDHF-mediated dilatation to acetylcholine. It is concluded that: (1) generations of free radical species accompany metabolic conversion of arachidonic acid, and (2) free radicals modulate vascular reactivity to EDHF in DOCA-salt-induced hypertension.
